PROJECT SUMMARY: GENE EDITING AND EPIGENOMICS CORE The C-SiG Gene Editing and Epigenomics Core provides current, emerging, and future gene editing and epigenomic technologies and expertise to center members. The organization and infrastructure of the core provides essential gene editing and epigenomics expertise and dedicated personnel to advise, interact with, provide reagents, and directly support C-SiG members in pursuit of the Specific Aims described below. The core will continue to be led by the Core Director, Dr. Stephen Ekker, who is a well-established molecular geneticist and gene editor and the Associate Core Director, Dr. Tamas Ordog, who is the founding Director of the Epigenomics Program of the Mayo Clinic Center for Individualized Medicine (CIM). The CIM Epigenomics Program develops, implements, and validates epigenomic technology and offering these methods to investigators. This resource will be leveraged to provide access to a broader segment of the C-SiG membership to state-of-the-art epigenomic methods at a discounted price, through a C-SiG supported technologist (50% FTE). The rapidly evolving disciplines of gene editing and epigenomics provide powerful tools to investigate the complex coordination of gene expression, which is modulated via a web of mechanistic relationships involving signaling pathways, transcription factors, and chromatin packaging. Epigenomics analysis when paired with genetic studies facilitated by gene editing technologies, greatly enhances identification of contributing molecular signaling pathways and environmental factors. Thus, provision of integrated access to gene editing and epigenomics expertise, tools, and assays, provides C-SiG members with a powerful and robust set of technologies to support digestive disease-related cell signaling research. Accordingly, we have defined and will pursue the following Specific Aims: i) Deliver state-of-the-art gene editing and epigenomics tools and assays that are needed by C-SiG members, including custom plasmids, custom nucleases and access to epigenomics assays including chromatin immunoprecipitation coupled with next generation sequencing (ChIP-seq assays), DNA immunoprecipitation-sequencing-based (DIP-seq); ii) Accelerate research by connecting members to gene editing and epigenomics-related consultation and educational opportunities such as seminars, journal clubs, and conferences; iii) Establish cutting-edge molecular tools and methods for custom genome and RNA editing including new DNA base editors, new RNA editing tools, and for epitranscriptomics (RNA modification assays). The C-SiG Gene Editing and Epigenomics Core services have been used by 53% of Center members and supported 29 publications during the past funding cycle.